Potassium Carbonate → HCID 68324151, compound

HRID 573683Notes

Reaction equation

HRID 573683 reaction equation
Br[C:2]1[C:10]2[C:5](=[N:6][C:7]([CH3:22])=[CH:8][C:9]=2[NH:11][S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)(=[O:14])=[O:13])[S:4][C:3]=1[C:23]1[CH:24]=[N:25][N:26](C(OC(C)(C)C)=O)[CH:27]=1.[CH3:35][O:36][C:37]1[CH:38]=[N:39][CH:40]=[C:41](B2OC(C)(C)C(C)(C)O2)[CH:42]=1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O.CN(C=O)C>[Cl:21][C:17]1[CH:16]=[C:15]([S:12]([NH:11][C:9]2[CH:8]=[C:7]([CH3:22])[N:6]=[C:5]3[S:4][C:3]([C:23]4[CH:24]=[N:25][NH:26][CH:27]=4)=[C:2]([C:41]4[CH:40]=[N:39][CH:38]=[C:37]([O:36][CH3:35])[CH:42]=4)[C:10]=23)(=[O:13])=[O:14])[CH:20]=[CH:19][CH:18]=1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 38661613-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 683240291,1-Dimethylethyl 4-(3-bromo-4-{[(3-chlorophenyl)sulfonyl]amino}-6-methylthieno[2,3-b]pyridin-2-yl)-1H-pyrazole-1-carboxylate

Product 1

HCID 68324151HCID 68324151, compoundYield 108.5%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 1,1-dimethylethyl 4-(3-bromo-4-{[(3-chlorophenyl)sulfonyl]amino}-6-methylthieno[2,3-b]pyridin-2-yl)-1H-pyrazole-1-carboxylate (Description 75) (100 mg, 0.171 mmol), 3-methoxy-5-pyridineboronic acid pinacol ester (81 mg, 0.343 mmol), potassium carbonate (71.0 mg, 0.514 mmol), tetrakis(triphenylphosphine)palladium(0) (4.95 mg, 4.28 μmol) and bis(triphenylphosphine)palladium(II) chloride (3.01 mg, 4.28 μmol) were weighed into a microwave vial. 1,4-Dioxane (1.5 mL), DMF (0.75 mL) and water (0.38 mL) were added and the mixture heated in a microwave at 110° C. for 30 min. At this point, both reaction mixtures were combined and concentrated. The residue was passed through an SCX cartridge, eluting with MeOH (100 mL) and then 2M NH3 in MeOH (150 mL). The basic methanolic solution was concentrated and purified by MDAP (acidic conditions), to give the title compound (95 mg). LCMS (A) m/z: 512 [M+1]+, Rt 0.88 min (acidic).

Workup

  1. customAt this point, both reaction mixtures
  2. concentrationconcentrated
  3. washeluting with MeOH (100 mL)
  4. concentrationThe basic methanolic solution was concentrated
  5. custompurified by MDAP (acidic conditions)

Sources & evidence

ORD record
ord-fe8ecb8d6464426faef4ee8e6ba1b862
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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